In 1977, Scacchi left UWA to return to England to pursue an acting career, studying at the Bristol Old Vic Theatre School, with Miranda Richardson and Amanda Redman. In 1982, she made her film debut in the German movie, Das Zweite Gesicht (The Second Face), and gave versatile performances in films, such as Heat and Dust (1983), The Ebony Tower (1984), The Coca Cola Kid (1985), White Mischief (1987), Presumed Innocent (1990), The Player (1992) and Country Life (1994). She turned down the role of Catherine Trammell in Basic Instinct (1992).
In 1996, she won an Emmy Award for her work as Empress Alexandra Fyodorovna of Russia in the television film, Rasputin: Dark Servant of Destiny, and was nominated for a Golden Globe and numerous other awards. In 2007, she received an Emmy Award nomination for Outstanding Supporting Actress in a Miniseries or a Movie for Broken Trail.
Scacchi is fluent in English, French, German and Italian, which has made her a popular choice for European casting directors and has been an asset when working for European directors and producers.
In May 2011, she appeared alongside Anita Dobson in the play Bette and Joan at London's Arts Theatre, directed by Bill Alexander, about the personal and professional relationship between Bette Davis and Joan Crawford